CYCLIC 3'-5' ADENOSINE MONOPHOSPHATE LEVELS IN THE RAT OLFACTORY TUBERCLE FOLLOWING IN VIVO MICROINJECTION OF DOPAMINE AND NEUROLEPTIC DRUGS (TRIFLUOPERAZINE)

Limbic forebrain structures such as the olfactory tubercle receive extensive innervation from mesolimbic neurons. Cells which lie post-synaptic to these terminals are rich in dopamine receptors. These receptors have been characterized by their stimulation (D1) or inhibition (D2) of adenylate cyclase. In Vitro studies of adenylate cyclase in homogenates have described this enzymes laminar distribution, neuronal localization and sensitivity to neuroleptic drugs.;Increases in cAMP levels in response to direct injection of DA were both time- and dose-dependent. Increases in cAMP levels from DA were up to five-fold basal levels. When co-injected with D2 selective doses of trifluoperazine, nearly two-fold stimulation of the DA only response (12-fold basal) was observed.;Tangential sectioning of the olfactory tubercle yielded a laminar distribution of the cAMP response due to DA injections and co-injections of DA and D2 selective doses of TFP. When D2 receptors were blocked with TFP, and DA was acting only at D1 receptors, the cAMP response in the cortical laminae of the olfactory tubercle revealed a distribution of cAMP closely paralleling that of in vitro dopamine-sensitive adenylate cyclase (DSAC) laminar distribution.;Other drugs such as promethazine, propranolol and thioridazine produced different localizations of cAMP response when co-injected with DA.;A method is described for stimulation of adenylate cyclase in vivo by direct injection of dopamine and other neuroactive substances (Life Sciences, Vol 35., pp 2145, 1984), the amplification of the cAMP response by D2 selective antagonism and the laminar location of both the DA-stimulated cAMP response and the amplified cAMP response by D2 selective neuroleptics.;This research demonstrates that DA and other neuroactive substances can stimulate cAMP production in vivo when injected directly into brain tissue. The agonist response of DA can be amplified by blocking inhibitory DA receptors. Further, the response can be localized anatomically to identified neuronal populations and neuronal fields. This will allow characterization of anatomical pathways which are important targets for the action of drugs useful in the treatment of schizophrenia and provide an in vivo model for testing new drugs.